**3. Neuropsychiatric SLE (NPSLE)**

#### **3.1 Clinical presentations**

#### *3.1.1 Criteria and classification*

Based on the manifestations, NPSLE can be categorized into focal and diffuse. Clinical presentations of NPSLE vary from mild impairment of cognition to altered mental status, psychosis, and seizure disorders. Headaches, cognitive deficits, and mood disorders are the most commonly found neuropsychological features in SLE. Also, epileptic disorders, cerebrovascular dysfunctions, neuropathic disease, and acute confusion conditions are the common presentations linked to NPSLE [17].

The American College of Rheumatology (ACR) introduced a consensus statement that classified 19 neuropsychiatric (NP) syndromes. These neuropsychiatric syndromes can be categorized into twelve central nervous systems (CNS) and seven peripheral nervous systems (PNS) syndromes. In addition, these were divided into diffuse neuropsychiatric diseases and focal nervous system disorders [18]. The frequency of these manifestations ranges from 0.08 to 80%. Some syndromes are more common (6.4%–80%), and the other syndromes are common (7%–20%), uncommon (0.6%–11%), or scarce (0.08%–2%). Neuropsychiatric manifestations including neuromyelitis optica spectrum disorder, chronic inflammatory demyelinating polyneuropathy, and small fiber neuropathy, are as well reported in SLE; however, these are not considered in this categorization. This categorization is not based on any precise pathological and physiological process: yet, it helps the diagnosis of SLE in the case of nervous system influence [19, 20].

#### *3.1.2 General NPSLE presentations*

Headaches, cognitive dysfunction, and psychiatric disorders (major depressive disorder (MDD), anxiety) are the most prevalent NPSLE symptoms. Neuropsychiatric manifestations usually develop in the initial stages of SLE. Previous evidence reported that up to 40% of neuropsychological presentations are detected within the initial year of being diagnosed with SLE. NPSLE manifestations can be devastating symptoms of SLE [21]. As mentioned above, NPSLE manifestations can be classified as CNS and/or PNS manifestations.

#### *3.1.3 Pediatric NPSLE*

In children, a recent work explored the presentations, therapy, and outcome of NPSLE cases. The charts of 185 children with SLE diagnosed from 1985 to 2005 in a medical center were investigated respectively. NPSLE was characterized by the ACR NPSLE descriptions. NPSLE was found in about a third of the cases. The average age of onset was 15.2 years. A fifth showed NP presentations when initially diagnosed with SLE. The most commonly observed NP findings were epileptic disorder (84.4%), cerebral infarction (28.1%), and psychosis (21.9%). Elevated average C3/C4 quantities, a reduced proportion of anti-dsDNA antibodies increased, and an amplified proportion of raised anticardiolipin antibodies were reported in NPSLE individuals compared to non-NPSLE individuals. NPSLE is common in SLE children. It is linked to heterogeneous presentations and a significant mortality rate [22].

#### *3.1.4 CNS manifestations of NPSLE*

#### *3.1.4.1 Depression*

Depressive disorder is the most frequent mood disturbance in NPLSE. Its prevalence over the course of life could reach about two-thirds of cases, however, mania is less frequent. Lately, evidence showed that depression in SLE is linked to several factors. High-dose prednisone was found most remarkable independent element, while global disease activity was not associated. Other influential elements were a new diagnosis of SLE, cutaneous problems, longitudinal myelitis, and belonging to an ethnic group other than Asia. Therefore, in certain cases, SLE-associated depressive condition is linked to adverse effects of treatment rather than with disease activity. Based on this notion, clinicians are encouraged to reduce prednisone doses or avoid its use [23]. A link between depressive disorders and exclusive antibodies produced against at NMDA receptor, ribosomal-P, and other neural epitopes has been found. More study is required to decipher the underpinnings of SLE-related depression and further therapy.

#### *3.1.4.2 Headache*

The association between SLE and headache has been well-researched, however, the findings were inconsistent. Although some previous reports have found enhanced *Lupus and the Nervous System: A Neuroimmunoloigcal Update on Pathogenesis and Management… DOI: http://dx.doi.org/10.5772/intechopen.107970*

headache occurrence in SLE cases, other experiments have not reported an elevation in the headache prevalence in comparison the healthy individuals.

Primary headaches, in particular tension-type headaches (TTH) and migraine, are frequent findings in NPSLE. However, secondary etiology of headache must be ruled out, such as cerebral venous sinus thrombosis, brain vasculitis, meningitis, and subarachnoid hemorrhage. The phrase 'SLE headache' is defined as a critical chronic headache for which narcotic painkillers are not effective. Lupus headache is defined as an element within the disease spectrum and therefore was classified as one of 19 neuropsychiatric diseases in ACR criteria for NPSLE [24].

#### *3.1.4.3 Seizure*

Generalized and focal seizures could occur in 10 to 20% of SLE cases. Seizures usually develop soon after the diagnosis of SLE [25].

#### *3.1.4.4 Cerebrovascular disease*

The occurrence of temporary ischemic attacks and stroke is increased among SLE patients [26]. Cerebrovascular accident in SLE is strongly related to the presence of aPL antibodies, Libman-Sacks endocarditis, accelerated atherosclerosis, and cardioembolism due to heart valvular abnormalities [25].

#### *3.1.4.5 Demyelinating syndromes*

Clinical findings of demyelination were reported in 0.3% of SLE cases. SLErelated-demyelination is not yet clearly understood. Therefore, notable investigation toward its diagnosis and management is required. These syndromes may include clinically isolated syndrome (CIS), could be similar to other CNS demyelinating syndromes (for instance, multiple sclerosis (MS)), result from medication, and, in certain conditions, the diagnosis could be made solely by long-term follow-up [27].

#### *3.1.4.6 Transverse myelitis*

Transverse myelitis is estimated to affect 1.5% of cases in SLE. Lately, researchers have linked transverse myelitis-SLE to aPL antibodies [28], thereby highlighting spinal cord degeneration as a result of thrombosis as an underlying mechanism. In certain situations, a similarity between Devic's disease with the existence of anti-NMO immunoglobulins is presumed. In the rest of the situations, transverse myelitis could turn into MS [25].

#### *3.1.4.7 Movement disorders*

Chorea is the most frequent movement problem in SLE and develops in 2 to 3% of SLE cases and this percentage is more in children, while ataxia, Parkinsonism, and hemiballismus are somewhat scarce symptoms in SLE patients. Chorea often occurs during the first years of SLE diagnosis and is found by aPL antibodies in up to 92% of patients [29, 30]. It has been proposed that such antibodies pass through the BBB, attach to nerve cells' antigens, and ultimately lead up to this symptom [31].

## *3.1.4.8 Aseptic meningitis*

Aseptic meningitis can be a neurological finding of ongoing SLE. Other etiology of aseptic meningitis, including pharmacotherapy, cancer, and infections are to be excluded [25].
